ERBB2 and breast carcinoma: Trastuzumab (Herceptin), the first anti-HER2 monoclonal antibody targeting the extracellular domain of the HER2 protein, has been an acknowledged treatment for both early stage and metastatic HER2-positive breast cancer for decades.129 Trastuzumab interferes with HER2 signaling in tumors via various mechanisms: inhibition of dimerization, antibody-dependent cellular cytotoxicity, receptor internalization and/or degradation, and suppression of the PI3K/AKT/mTOR signaling cascades.